1. Field of the Invention
The present invention relates generally to methods for promoting angiogenesis in tissue surrounding body lumens. More particularly, the present invention relates to methods for promoting angiogenesis in tissue surrounding coronary and peripheral arteries in order to treat ischemia.
Coronary artery disease usually results from the deposition of atheromas in the large and medium-sized arteries supplying the heart. Such blockages of the coronary arteries can in turn cause myocardial ischemia which is a condition characterized by limited and/or irregularly distributed blood flow from the coronary arteries to heart tissue. In severe cases, myocardial ischemia can result in myocardial infarction (heart attack) and sudden cardiac death. Angina pectoris is a chronic condition associated with myocardial ischemia and characterized by chest discomfort as a result of vigorous and in some cases even mild exertion.
Angina pectoris can be treated by the administration of drugs, such as .beta.-adrenergic blocking agents and vasodilators, including nitroglycerin, amyl nitrite, nitrates, and calcium antagonists. While effective for short-term treatment, such drugs are ineffective at treating the arterial blockages responsible for the underlying coronary artery disease. To treat the arterial blockages, various surgical and catheter-based protocols have been developed. The most effective is probably coronary artery bypass surgery, where bypass grafts are surgically implanted around blockages in the coronary arteries. While very effective, coronary artery bypass surgery is highly invasive and results in significant patient morbidity and mortality. Catheter-based interventions, such as balloon angioplasty, laser angioplasty, and atherectomy, are considerably less invasive, but are also less effective, frequently resulting in abrupt closure or restenosis following the intervention.
For these reasons, it would be desirable to provide alternative methods for treating coronary artery disease, where the methods are both effective and minimally invasive. It would be particularly desirable to provide additional catheter-based interventions for treating coronary artery blockages in order to enhance blood perfusion to heart muscle beyond such blockages. More specifically, it would be desirable to provide methods and systems for delivering active agents for promoting angiogenesis to enhance collateral flow to ischemic tissue beds.
2. Description of the Background Art
Periadvential and systemic delivery of bFGF to promote angiogenesis in cardiac tissue are described in Cuevas et al. (1993) Surg. Neurol. 39: 380-384; Selke et al. (1994) Am. J. Physiol. 267: H1303-1311; Harada et al. (1994) J. Clin. Invest. 94: 623-630; Edelman et al. (1993) Proc. Natl. Acad. Sci. USA 90: 1513-1517; and Whalen et al. (1989) Growth Factors 1: 157-164. The effect of direct coronary infusion of bFGF into swine hearts is described in Battler et al. (1993) J. Am. Coll. Cardiol. 22: 2001-2006.
The use of intravascular catheters for delivering particular drugs and classes of drugs is described in U.S. Pat. Nos. 5,180,366; 5,171,217; 5,049,132; and 5,021,044; and PCT Publications WO 93/08866 and WO 92/11895. Riessen et al. (1994) JACC 23: 1234-1244 is a review article discussing the use of catheters and stents for the local delivery of therapeutic agents into the blood vessel wall.
A preferred infusion catheter for delivering an angiogenic factor in accordance with the methods of the present invention is described in copending application Ser. No. 08/473,800, assigned to the assignee of the present invention, filed on Jun. 7, 1995, the full disclosure of which is incorporated herein by reference. This copending application teaches that the catheter may be used for the intravascular delivery of anti-restenotic, anti-proliferative, thrombolytic, fibrinolytic, and other agents useful in connection with angioplasty treatment in a patient's coronary vasculature.